Figure 4. Strategies for miRNA-based therapies.

Blocking oncogenic miRNAs can be achieved by the use of antisense oligonucleotides, miRNA sponges, miRNA-mask and small RNA inhibitors^91-99. (A) Antisense oligonucleotides can bind to the target miRNAs following the Watson and Crick complementarities and induces either degradation or duplex formation^101,107. The three most common oligonucleotide modification structures are shown; Locked nucleic acid (LNA), 2-0-methyl (2-0-ME) and phosphorothiolate (PS)^101,107. (B) The miR-mask oligonucleotides are synthetic oligonucleotides complementary to the 3' UTR target mRNA that compete with endogenous miRNAs for its target⁹⁸. Therefore, miR-mask is able to block oncogenic miRNA deleterious functions at the target level. (C) The miRNA sponges are oligonucleotide constructs with multiple complementary miRNA binding sites (in tandem) to the target miRNA⁹⁷. When introduced to the cell, sponges will “soak” endogenous miRNAs (Red oligos), decreasing the expression levels of an oncogenic miRNA. (D) Small molecule miRNA inhibitors regulate miRNA expression at transcriptional level⁹⁹. Restoring down-regulated miRNA expression could be achieved by (E) using synthetic miRNAs (miRNA mimics) or (F) by inserting genes coding for miRNAs into viral constructs, such as the adeno associated viral vectors ^100-101.